Case Report

Pratap Singh1, Sanjay

Progressive Disseminated Histoplasmosis
Kumar2, Pramila in an Immunocompetent Host with
Dharmshaktu3, Dinesh
Meher4, Vijay Kumar5 Reversible CD4 Lymphocytopenia
1
Associate Professor,
3,4
Resident, Department of
Abstract
5
Medicine, Associate
Professor, Department of We report an 18-year-old male patient presented to us with complaints of fever and
Pathology, Dr Ram Manohar progressive weight loss for past 4 months. On examination, he also had multiple
Lohia Hospital & PGIMER, umbilicated papular to nodular lesions over his chin and forehead region. Blood
New Delhi. count revealed anemia with leukopenia. An excisional biopsy of the skin lesion was
2
Associate Professor, suggestive of cutaneous histoplasmosis. On further investigations for anemia and
Department of Medicine, leukopenia, he was found to have bone marrow histoplasmosis on trephine biopsy.
Lady Hardinge Medical Patient’s serology for HIV I and II was negative but his CD4 counts were low. Patient
College, Dr Ram Manohar received amphotericin B and itraconazole. He showed remarkable improvement in
Lohia Hospital & PGIMER,
New Delhi.
his general condition and blood counts. A repeat CD4 count done at 4 months of
treatment was also normal. Progressive disseminated histoplasmosis (PDH)
Correspondence to: presenting as cutaneous lesions in an immunocompetent host is very rare and has
Dr Sanjay Kumar, been reported in a few cases only.
Department of Medicine,
Lady Hardinge Medical Keywords: Progressive disseminated histoplasmosis, reversible CD4 depletion.
College, Dr Ram Manohar
Lohia Hospital & PGIMER,
New Delhi.
Background

E-mail Id: drpratapsingh@ Histoplasmosis is a fungal infection and prevalent worldwide, in which Ohio and
yahoo.co.in Mississippi river valleys of North America have the highest prevalence. There are a
few case reports of this fungal infection from non-endemic regions too.1-3 In India,
histoplasmosis has been reported in large numbers from eastern states like West
Bengal,4,5 and a few cases from southern states as well.6,7 Other regions of the
country rarely see any cases of histoplasmosis. Histoplasmosis is most commonly
seen in immunosuppressed patients8 but there are a few case reports in
immunocompetent hosts as well.9,10

Case Presentation
An 18-year-old, unmarried male patient, resident of Delhi (central India), presented
to our hospital with complaints of low-grade prolonged fever, loss of appetite and
weight loss of 10 kg in last 4 months. No history of high-risk behavior, promiscuous
sexual activities or blood transfusion in the past. He was a non-smoker and non-
alcoholic. There was also no history of exposure to bird’s dropping or recent travel to
How to cite this article:
endemic parts of the country. There was no past history of tuberculosis, diabetes
Singh P, Kumar S, mellitus or any other chronic systemic illness.
Dharmshaktu P et al.
Progressive Disseminated On examination, the patient was of thin-built male with stable vitals. There were
Histoplasmosis in an multiple umbilicated papular to nodular lesions over forehead and chin, without any
Immunocompetent Host erythema or tenderness (Fig. 1).
with Reversible CD4
Lymphocytopenia. J Adv Res He had pallor, but no icterus, clubbing, cyanosis, or peripheral lymphadenopathy.
Med 2016; 3(2&3): 14-17. The abdominal examination revealed mild, non-tender hepatosplenomegaly, but no
ISSN: 2349-7181
free fluid. The chest and cardiovascular examination did not reveal any abnormality.

© ADR Journals 2016. All Rights Reserved.

J. Adv. Res. Med. 2016; 3(2&3) Singh P et al.

Figure 1.Multiple Papular to Nodular Skin Lesions over Chin Region

Investigations necrosis. Ultrasound abdomen revealed

The blood count revealed bicytopenia (hemoglobin 7.2
gm/dL, total leucocyte count 3200/mm3 with polymorph
75%, lymphocyte 20%, eosinophil 3% and monocyte 2%.
Platelet count was 2.5 lac/mm3 and erythrocyte
sedimentation rate (ESR) was 38 mm in first hour. The
anemia was normocytic normochromic on peripheral
smear examination. The biochemical tests revealed a
total protein of 7.5 gm/dL, albumin 2.5 gm/dL, globulin
5.0 gm/dL with reversal of albumin-globulin ratio. The
serum LDH level was 308 IU/L. Other routine
biochemical tests, like bilirubin, transaminases, alkaline
phosphatase, urea, and creatinine were normal. The
blood culture and urine culture were sterile after 48
hours of incubation. Sputum examination did not reveal
any organism by Gram’s or acid-fast staining. Chest X-
ray was normal; however, the contrast enhanced CT
chest revealed left hilar and pre-tracheal
lymphadenopathy with foci of calcification but no
hepatosplenomegaly. CECT abdomen ruled out
involvement of adrenal glands. Serum protein
electrophoresis revealed hypergammaglobulinemia.
Skin biopsy showed ill-defined non-caseating
granulomas with macrophages showing yeast forms of
histoplasma capsulatum (Fig. 2). Fungal stain was also
positive. Bone marrow aspiration and biopsy showed
normal hematopoiesis with presence of yeast forms of
histoplasma capsulatum (Figs. 3, 4).
The patient was thus diagnosed as a case of progressive
disseminated histoplasmosis (PDH). He underwent
further investigations to look for any underlying
immune dysfunction. Serology for HIV I and II was
negative on two occasions while the CD4 count was low
at 161/µL (normal 500-1200 cells/mm3). The bone
marrow aspirate cultures were also positive for
histoplasma capsulatum at 1 month.

Figure 2.Multiple Ill-Defined Non-caseating Granulomas Present with Yeast Forms of Histoplasma Capsulatum
(Arrow) in the Skin Biopsy

15 ISSN: 2349-7181
Singh P et al. J. Adv. Res. Med. 2016; 3(2&3)

Figure 3.Normal Hematopoiesis and Macrophages with Yeast Form of Histoplasma

Capsulatum in Bone Marrow Aspiration

Figure 4.Yeast Forms within Macrophages on Silver Methanamine and PAS Stain on Bone Marrow Biopsy (Arrow)

Differential Diagnosis he was discharged on oral Itraconazole. He visited again

Patient presenting with longstanding fever, loss of
appetite, significant weight loss, bicytopenia and
hepatosplenomegaly in India, the first provisional
diagnosis that was considered was disseminated
tuberculosis. Other differential would include visceral
leishmaniasis, lymphoma, leukemia, and HIV-AIDS. Once
we got a report of skin and bone marrow biopsy little
was of doubt that we were dealing with progressive
disseminated histoplasmosis. The HIV report came out
to be negative, but the CD4 count was low. Due to lack
of sufficient funds, we could not investigate further to
rule out primary immunodeficiency.
Treatment
3 weeks later with fading skin lesions and was on
regular follow up. At fourth month, the CD4 count was
also repeated to exclude the possibility of idiopathic
CD4 cell lymphocytopenia which was normal at 584
cells/mm3. An extensive workup for primary
immunodeficiency states could not be done due to the
non-availability of the same at our hospital and also
because the patient belongs to a poor social strata and
could not afford expensive tests.
Outcome and Follow-Up
The patient responded very well to the treatment and,
till today, has not shown any new or recurrent infection
on follow up.

Patient was started on intravenous amphotericin B at a Discussion

dose of 0.5 mg/kg/day with gradual escalation to 1
mg/kg/day for 4 weeks and then oral itraconazole at a Histoplasmosis is a fungal infection caused by
dose of 200 mg daily which was continued for 6 months. histoplasma capsulatum var capsulatum and
There was marked improvement of his symptoms and histoplasma capsulatum varduboisii. Our patient

ISSN: 2349-7181 16
J. Adv. Res. Med. 2016; 3(2&3)
presented with skin lesion, the biopsy of which
confirmed histoplasma. Similar skin-colored, papulo-
nodular lesions have been seen in literature. However
the lesions were present on head, trunk and extremity.
It was also associated with nodulo-ulcerative growth in
hard palate.11 Patient living with HIV and AIDS may
present with reddish papules and pustules in the skin of
the scalp, face, back, thighs, abdomen, palms, and
soles.12 Our patient also had bicytopenia and
hepatosplenomegaly, which is a feature of infection of
reticuloendothelial system and bone marrow
involvement.13 Our patient was negative for HIV and had
low CD4 lymphocyte count at presentation. There have
been a few case reports, from various parts of the
world, of immunocompetent patients presenting with
infections which are normally seen in HIV-AIDS patients
or in patients with immunosuppression.14-20 These
infections are, however, associated with idiopathic low
CD4 lymphocytopenia or dysfunction of T helper cells. In
our patient, we suspected this condition but the repeat
count after 3 weeks came out to be normal; hence, this
condition was ruled out.
Learning Points
Progressive disseminated histoplasmosis should be
considered in a immunocompetent host. It may be seen
in HIV-AIDS negative individuals with low CD4 count.
Low CD4 count is reversible on treatment of
histoplasmosis with anti-fungal therapy.
Conflict of Interest: None
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Date of Submission: 10th Sep. 2016
Date of Acceptance: 27th Sep. 2016
ISSN: 2349-7181